Evidence map›Paper›PMID 40577120›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Retinoic acid receptor assembly dynamics governs dual functions in cochlear organogenesis.

Saikat Chakraborty, Shuze Wang, Jack Ruhala, Brett Mehling, Jie Liu, Joerg Waldhaus

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Retinoic acid receptor assembly dynamics governs dual functions in cochlear organogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Saikat Chakraborty *Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0002-2908-7205
Shuze Wang *Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0003-1157-1311
Jack RuhalaDepartment of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109.
Brett MehlingDepartment of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109.ORCID 0009-0006-1763-2911
Jie LiuGilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0002-9504-0587
Joerg WaldhausDepartment of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0002-6498-661X

Funding

Patterning of the Cochlear Apex-to-Base AxisR01DC021687 · NIDCD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joerg Waldhaus · 2024 to 2026
$1.4M
HHS | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD) R01DC021687NIDCD NIH HHS R01 DC021687
6 · The paper itself

Abstract

Retinoic acid (RA) is a morphogen that contributes to inner ear development. Gain and loss of function experiments have indicated retinoic acid's critical role in cochlear hair cell development. However, the underlying molecular mechanisms are unclear. Here, we hypothesized that RA receptor alpha (RARA) has a dual role in cochlear organogenesis: First, during embryonic development, in the presence of RA, RARA functions as a transcriptional activator that induces prosensory gene expression in progenitor cells and supports differentiation of the organ of Corti; later during postnatal development, when RA is absent, the function of RARA switches, thereby repressing prosensory genes in postnatal hair cells and hindering trans-differentiation into supporting cells. This hypothesis was supported by demonstration that RARA forms a complex with either the coactivator NCOA1 or the corepressor NCOR1 depending on the developmental stage. In addition, modulation of RA levels was found to govern recruitment of the coactivator and corepressor to the RARA complex, and the expression of prosensory genes was validated to depend on RARA complex composition. Together, our results provide insights supporting the potential of harnessing RA signaling to induce prosensory progenitors in stem cell-based strategies for hearing loss.

Indexed as

CochleaOrganogenesisReceptors, Retinoic AcidAnimalsCell DifferentiationGene Expression Regulation, DevelopmentalHair Cells, AuditoryMiceNuclear Receptor Coactivator 1Retinoic Acid Receptor alphaSignal TransductionTretinoinNuclear Receptor Coactivator 1Receptors, Retinoic AcidRetinoic Acid Receptor alphaTretinoinorgan of Cortiprosensory progenitorsRARAreceptor complexretinoic acid

Identifiers

PMID40577120
PMCPMC12232719

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.